Immunogenetics of Aging

  • R. L. Walford
  • G. S. Smith
  • P. J. Meredith
  • K. E. Cheney


As recently as the late 1960s, a major drawback to an immunological interpretation of aging seemed to be that animals below the vertebrate level did not possess true immunological systems (Walford, 1969). It has been clearly demonstrated by now, however, that at least in echinoderms, annelids, and coelenterates, specific immunocompetence with components of memory or immunorecognition systems or both, exists (Hildemann, 1978). At the same time, it is known that life span may vary independently of phylogenetic or evolutionary position (Hildemann, 1978), and that animals high on the evolutionary scale may display much longer or shorter life spans than animals relatively low on the scale. Broad-ranging possibilities for immunogenetic investigations of aging are therefore evident. Unfortunately, those invertebrates that have been investigated immunologically have not been much studied genetically, and those for which abundant genetic information is available—arthropods, for example—have not been subjected to refined immunological scrutiny. The one form of immune response that is probably common to all metazoa is the recognition of self from nonself, demonstrable experimentally by transplant rejection. Immu-nogenetic information relevant to aging in the usual sense, i.e., variation within the species rather than comparisons between species, derives almost entirely from studies of higher animals subjected to laboratory experimentation or clinical observation, such as the mouse, man, rat, guinea pig, and hamster.


Major Histocompatibility Complex Accelerate Aging Purify Protein Derivative Congenic Mouse Pokeweed Mitogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations used in this chapter


cell-mediated lymphocytotoxicity





(Ir gene)

immune respone gene

(L chain)

light chain




major histocompatibility complex


mixed lymphocytereaction




purified protein derivative




sheep red blood cells


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  1. Bevan, M. J., 1975, Interaction antigens detected by cytotoxic T-cells with the major histo-compatibility complex as modifier, Nature (London) 256:419.CrossRefGoogle Scholar
  2. Blumenthal, H. T., and Berns, A. W., 1964, Autoimmunity and aging, Adv. Gerontol. Res. 1:289.Google Scholar
  3. Comfort, A., 1964, Ageing: The Biology of Senescence, Holt, Rinehart & Winston, New York.Google Scholar
  4. Cunningham, A. J., 1976, Self-tolerance maintained by active suppressor mechanisms, Transplant. Rev. 31:23.PubMedGoogle Scholar
  5. Cutler, R. G., 1975, Evolution of human longevity and the genetic complexity governing aging rate, Proc. Natl. Acad. Sci. U.S.A. 72:4664.PubMedCrossRefGoogle Scholar
  6. Datta, S. K., and Schwartz, R. S., 1976, Genetics of expression of xenotropic virus and autoimmunity in NZB mice, Nature (London) 263:412.CrossRefGoogle Scholar
  7. Doherty, P. C., and Zinkernagel, R. M., 1975, A biological role for the major histocompatibility antigens, 2:1406.Google Scholar
  8. Fabris, N., Pierpaoli, W., and Sorkin, E., 1972, Lymphocytes, hormones, and aging, Nature (London) 240:557.CrossRefGoogle Scholar
  9. Franklin, E. C., and Zucker-Franklin, D., 1972, Current concepts of amyloid, Adv. Immunol. 15:249.PubMedCrossRefGoogle Scholar
  10. Gajdusek, D. C., 1972, Slow virus infection and activation of latent infections in aging, Adv. Gerontol. Res. 4:201.Google Scholar
  11. Gerbase-DeLima, M., Wilkinson, J., Smith, G. S., and Walford, R. L., 1974, Age-related decline in thymic-independent immune function of a long-lived mouse strain, J. Gerontol. 29:261.PubMedGoogle Scholar
  12. Gerbase-DeLima, M., Meredith, P., and Walford, R. L., 1975a, Age-related changes including synergy and suppression in the mixed lymphocyte reaction in long-lived mice, Fed. Proc. Fed. Am. Soc. Exp. Biol. 34:159.Google Scholar
  13. Gerbase-DeLima, M., Liu, R. K., Cheney, K. E., Mickey, R., and Walford, R. L., 1975b Immune function and survival in a long-lived mouse strain subjected to undernutrition, Gerontologia 21:184.PubMedCrossRefGoogle Scholar
  14. Good, R. A., and Yunis, E., 1974, Association of autoimmunity, immunodeficiency and aging in man, rabbits, and mice, Fed. Proc. Fed. Am. Soc. Exp. Biol. 33:2040.Google Scholar
  15. Goodman, S. A., and Makinodan, T., 1975, Effect of age on cell-mediated immunity in long-lived mice, Clin. Exp. Immunol. 19:533.PubMedGoogle Scholar
  16. Hildemann, W. H., 1970, Components and concepts of antigenic strength, Transplant Rev. 3:5.Google Scholar
  17. Hildemann, W. H., 1978, Phylogenetic and immunogenetic aspects of aging, in: Genetic Effects on Aging, Birth Defects: Orig. Artie. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York (in press).Google Scholar
  18. Hung, C., Perkins, E. H., and Yang, W., 1975, Age-related refractoriness of PHA-induced lymphocyte transformation. II. 125 I-PHA-binding to spleen cells from young and old mice, Mech. Ageing Dev. 4:103.PubMedCrossRefGoogle Scholar
  19. Kay, M. M. B., 1978, Immunological aging patterns: Effect of parainfluenza type 1 virus infection on aging mice of 8 strains and hybrids, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York (in press).Google Scholar
  20. Kishimoto, S., Takahama, T., and Mizumachi, H., 1976, In vitro immune response to the 2,4,6-trinitrophenyl determinant in aged C57B1/6J mice: Changes in the humoral immune response to and avidity for the TNP determinant and responsiveness to LPS effect with aging, J. Immunol. 116:294.PubMedGoogle Scholar
  21. Konen, T. G., Smith, G. S., and Walford, R. L., 1973, Decline in mixed lymphocyte reactivity of spleen cells from aged mice of a long-lived strain, J. Immunol. 110:1216.PubMedGoogle Scholar
  22. Kunstyr, I., and Leuenberger, H. W., 1975, Gerontological data of C57BL/6J mice. I. Sex differences in survival curves, J. Gerontol. 30:157.PubMedGoogle Scholar
  23. MacKay, I. R., 1972, Ageing and immunological function in man, Gerontologia 18:239.CrossRefGoogle Scholar
  24. Makinodan, T., Perkins, E. H., and Chen, M. G., 1971, Immunological activity of the aged, Adv. Gerontol. Res. 3:171.PubMedGoogle Scholar
  25. Martin, G. M., 1978, Genetic syndromes in man with potential relevance to the pathobiology of aging, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York (in press).Google Scholar
  26. Mathies, M., Lipps, L., Smith, G. S., and Walford, R. L., 1973, Age-related decline in response to phytohemagglutinin and pokeweed mitogen by spleen cells from hamsters and long-lived mouse strain, J. Gerontol. 28:425.PubMedGoogle Scholar
  27. Meredith, P., and Walford, R. L., 1977, Effect of age on response to T and B cell mitogens in mice congenic at the H-2 region, Immunogenetics 5:109.CrossRefGoogle Scholar
  28. Mittal, K. K., 1976, The HLA polymorphism and susceptibility to disease, Vox Sang. 31:161.PubMedCrossRefGoogle Scholar
  29. Naor, D., Bonavida, B., and Walford, R. L., 1976, Autoimmunity and aging: The age-related response of mice of a long-lived strain to trinitrophenylated syngeneic mouse red blood cells, J. Immunol. 117:2204.PubMedGoogle Scholar
  30. Palmer, D. W., Dauphinee, M. J., Murphy, E., and Talal, N., 1976, Hyperactive T cell function in young NZB mice: Increased proliferative response to allogeneic cells, Clin. Exp. Immunol. 23:578.PubMedGoogle Scholar
  31. Popp, D. M., 1978, Use of congenic mice to study the genetic basis of degenerative disease, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York (in press).Google Scholar
  32. Rubenstein, P., Suciu-Foca, N., Nicholson, J. F., Fotino, M., Molinaro, A., Harisiadis, L., Hardy, M. A., Reemtsma, K., and Allan, F. H., Jr., 1976, The HLA system in the families of patients with juvenile diabetes mellitus, J. Exp. Med. 143:1277.CrossRefGoogle Scholar
  33. Sacher, G. A., 1959, Relation of lifespan to brain weight and body weight in mammals, Ciba Found. Colloq. Ageing 5:115.Google Scholar
  34. Segre, D., and Segre, M., 1976, Humoral immunity in aged mice. II. Increased suppressor T cell activity in immunologically deficient old mice, J. Immunol. 116:735.PubMedGoogle Scholar
  35. Shreffler, D. C., 1977, The H-2 model: Genetic control of immune functions, in: HLA and Disease (J. Dausset and A. Svejgaard, eds.), Munksgaard, Copenhagen.Google Scholar
  36. Siegal, B. V., Braun, M., and Morton, J. I., 1972, Detection of antinuclear antibodies in NZB and other mouse strains, Immunology 22:457.Google Scholar
  37. Smith, G. S., and Watford, R. L., 1978, Influence of the H-2 and H-1 histocompatibility systems upon lifespan and spontaneous cancer incidences in congenic mice, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York (in press).Google Scholar
  38. Smith, G. S., Walford, R. L., and Mickey, M. R., 1973, Lifespan and incidence of cancer and other diseases in selected long-lived inbred mice and their F1-hybrids, J. Natl. Cancer Inst. 50:1195.PubMedGoogle Scholar
  39. Storer, J. B., 1966, Longevity and gross pathology at death in 22 inbred mouse strains, J. Gerontol. 21:404.PubMedGoogle Scholar
  40. Svejgaard, A., Hange, M., Jersild, C., Platz, P., Ryder, L. P., Nielsen, L. S., and Thomsen, M., 1975a, The HLA system: An introductory survey, Mongr. Hum. Genet., No. 7.Google Scholar
  41. Svejgaard, A., Platz, P., Ryder, L. P., Nielsen, L. S., and Thomsen, M., 1975b, HLA and disease associations—A survey, Transplant. Rev. 22: 3.PubMedGoogle Scholar
  42. Talal, N., 1976, Disordered immunologie regulation and autoimmunity, Transplant. Rev. 31:240.PubMedGoogle Scholar
  43. Talal, N., and Steinberg, A. D., 1974, The pathogenesis of autoimmunity in New Zealand black mice, in: Current Topics in Microbiology and Immunology, p. 79, Springer-Verlag, New York.CrossRefGoogle Scholar
  44. Thomsen, M., Platz, P., Anderson, O. C., Christy, M., Lyngsoe, J., Nerup, J., Rasmussen, K., Ryder, L. P., Nielsen, L. S., and Svejgaard, A., 1975, MLC typing in juvenile diabetes mellitus and idiopathic Addison’s disease, Transplant. Rev. 22:125.PubMedGoogle Scholar
  45. Vracko, R., and Benditt, E. P., 1975, Restricted replicative lifespan of diabetic fibroblasts in vitro: Its relation to microangiopathy, Fed. Proc. Fed. Am. Soc. Exp. Biol. 34:68.Google Scholar
  46. Watford, R. L., 1969, The Immunologie Theory of Aging, Munksgaard, Copenhagen.Google Scholar
  47. Watford, R. L., 1970, Antibody diversity, histocompatibility systems, disease states, and aging, Lancet 2:1226.CrossRefGoogle Scholar
  48. Watford, R. L., 1974, The immunologie theory of aging: Current status, Fed. Proc. Fed. Am. Soc. Exp. Biol. 33:2020.Google Scholar
  49. Watford R. L., 1977, Human B-cell alloantigens: Their medical and biological significance, in: HLA System: New Aspects, (G. B. Ferrara, ed.), pp. 105–127, Elsevier-North-Holland Publishing Co., Amsterdam.Google Scholar
  50. Watford, R. L., and Sjaarda, J. R., 1964, Increase of thioflavine-T-staining material (amyloid) in human tissues with age, J. Gerontol. 19:57.Google Scholar
  51. Watson, J., and Riblet, R., 1974, Genetic control of response to bacterial lipopolysaccharide in mice, J. Exp. Med. 140:1147.PubMedCrossRefGoogle Scholar
  52. Whittingham, S., Mathews, J. D., MacKay, I. R., Stocks, A. E., Ungar, B., and Martin, F. I. R., 1971, Diabetes mellitus, autoimmunity and ageing, Lancet 1:763.PubMedCrossRefGoogle Scholar
  53. Yunis, E. J., and Greenberg, L. J., 1978, Genetic control of autoimmune disease and aging immune responses, in: Genetic Effects on Aging, Birth Defects: Orig. Artic. Ser. (D. Bergsma and D. E. Harrison, eds.), The National Foundation-March of Dimes, New York.Google Scholar
  54. Yunis, E. J., Fernandes, G., Teague, P. O., Stutman, O., and Good, R. A., 1972, The thymus, autoimmunity and the involution of the lymphoid system, in: Tolerance, Autoimmunity, and Aging (M. M., Sigel, ed.), pp. 62-119.Google Scholar
  55. Yunis, E. J., Fernandes, G., and Greenberg, W. J., 1973, Immune deficiency, autoimmunity and aging, in: Immunodeficiency Workshop, Birth Defects: Orig. Artic. Ser., No. 11, p. 85, Plenum Press, New York.Google Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • R. L. Walford
    • 1
  • G. S. Smith
    • 1
  • P. J. Meredith
    • 1
  • K. E. Cheney
    • 1
  1. 1.Department of PathologyUniversity of CaliforniaLos AngelesUSA

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